Noninvasive Molecular Imaging of the Enhanced Permeability and Retention Effect by 64 Cu-Liposomes: In vivo Correlations with 68 Ga-RGD, Fluid Pressure, Diffusivity and 18 F-FDG.

Autor: Børresen B; Department of Veterinary Clinical Sciences, Faculty of Health and Medical Sciences, University of Copenhagen, Frederiksberg C 1870, Denmark., Hansen AE; Cluster for Molecular Imaging, Department of Biomedical Sciences, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen N 2200, Denmark.; DTU Health Technology, Center for Nanomedicine and Theranostics, Technical University of Denmark, Lyngby, Kgs 2800, Denmark., Fliedner FP; Cluster for Molecular Imaging, Department of Biomedical Sciences, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen N 2200, Denmark., Henriksen JR; DTU Health Technology, Center for Nanomedicine and Theranostics, Technical University of Denmark, Lyngby, Kgs 2800, Denmark., Elema DR; DTU Health Technology, Center for Nanomedicine and Theranostics, Technical University of Denmark, Lyngby, Kgs 2800, Denmark.; DTU Health Technology, The Hevesy Laboratory, Center for Nuclear Technologies, Technical University of Denmark, Roskilde, 4000, Denmark., Brandt-Larsen M; Department of Clinical Physiology, Nuclear Medicine and PET, Copenhagen University Hospital, Copenhagen Ø 2100, Denmark., Kristensen LK; Cluster for Molecular Imaging, Department of Biomedical Sciences, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen N 2200, Denmark.; DTU Health Technology, Center for Nanomedicine and Theranostics, Technical University of Denmark, Lyngby, Kgs 2800, Denmark.; DTU Health Technology, The Hevesy Laboratory, Center for Nuclear Technologies, Technical University of Denmark, Roskilde, 4000, Denmark.; Department of Clinical Physiology, Nuclear Medicine and PET, Copenhagen University Hospital, Copenhagen Ø 2100, Denmark.; Minerva Imaging, Copenhagen N 2200, Denmark., Kristensen AT; Department of Veterinary Clinical Sciences, Faculty of Health and Medical Sciences, University of Copenhagen, Frederiksberg C 1870, Denmark.; Cluster for Molecular Imaging, Department of Biomedical Sciences, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen N 2200, Denmark.; DTU Health Technology, Center for Nanomedicine and Theranostics, Technical University of Denmark, Lyngby, Kgs 2800, Denmark.; DTU Health Technology, The Hevesy Laboratory, Center for Nuclear Technologies, Technical University of Denmark, Roskilde, 4000, Denmark.; Department of Clinical Physiology, Nuclear Medicine and PET, Copenhagen University Hospital, Copenhagen Ø 2100, Denmark.; Minerva Imaging, Copenhagen N 2200, Denmark., Andresen TL; DTU Health Technology, Center for Nanomedicine and Theranostics, Technical University of Denmark, Lyngby, Kgs 2800, Denmark., Kjær A; Cluster for Molecular Imaging, Department of Biomedical Sciences, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen N 2200, Denmark.; Department of Clinical Physiology, Nuclear Medicine and PET, Copenhagen University Hospital, Copenhagen Ø 2100, Denmark.
Jazyk: angličtina
Zdroj: International journal of nanomedicine [Int J Nanomedicine] 2020 Nov 02; Vol. 15, pp. 8571-8581. Date of Electronic Publication: 2020 Nov 02 (Print Publication: 2020).
DOI: 10.2147/IJN.S239172
Abstrakt: Background: The accumulation of liposome encapsulated chemotherapy in solid cancers is dependent on the presence of the enhanced permeability and retention (EPR) effect. Positron emission tomography (PET) imaging with a liposome encapsulated radioisotope, such as liposome encapsulated Cu-64 ( 64 Cu-liposome) may help to identify tumors with high liposome accumulation, and thereby stratify patients based on expected benefit from liposomal chemotherapy. However, intravenous administration of liposomes without a cytotoxic content is complicated by the accelerated blood clearance (ABC) phenomenon for succeeding therapeutic liposome dosing. Alternative markers for assessing the tumor's EPR level are therefore warranted.
Materials and Methods: To increase our understanding of EPR variations and to ultimately identify an alternative marker for the EPR effect, we investigated the correlation between 64 Cu-liposome PET/CT (EPR effect) and 68 Ga-RGD PET/CT (neoangiogenesis), 18 F-FDG PET/CT (glycolysis), diffusion-weighted MRI (diffusivity) and interstitial fluid pressure in two experimental cancer models (CT26 and COLO 205).
Results: 64 Cu-liposome and 68 Ga-RGD SUV max displayed a significant moderate correlation, however, none of the other parameters evaluated displayed significant correlations. These results indicate that differences in neoangiogenesis may explain some EPR variability, however, as correlations were only moderate and not observed for SUV mean , 68 Ga-RGD is probably insufficient to serve as a stand-alone surrogate marker for quantifying the EPR effect and stratifying patients.
Competing Interests: Financial support was provided by the Danish Strategic Research Council (NABIIT) ref. 2106-07-0033, the Lundbeck Foundation and the European Council (ERC grant). Annemarie Thuri Kristensen reports grants from Danish Technical University, during the conduct of the study; grants from Novo Nordisk A/S, grants from Copenhagen ZOO, grants from Independent Research Fund Denmark, outside the submitted work. The authors report no other potential conflicts of interest in this work.
(© 2020 Børresen et al.)
Databáze: MEDLINE
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